Considerable variation has been reported for placental-type alkaline phosphatase in cancer patients and in placentae, which in the latter case is allelic. In this study, immunochemical reagents will be developed to identify variant-specific structural determinants, using both absorbed rabbit antisera and monoclonal antibodies. Efforts to define the structure of the enzyme immunochemically will be complemented by analysis of specific peptides obtained from variant enzymes, including active site peptides, peptides containing carbohydrate side-chains, variant-specific peptides and peptides specifically reactive with variant-specific antibodies. The objective of these studies is to identify structural differences that account for the documented differences in properties of individual variant enzymes. The immunochemical reagents specifically reactive with individual variant enzymes will also be used to measure the amount of specific variant enzymes present in human tumors, cultured cells and tumor xenografts mintained in "nude" mice. This will permit us to measure whether placental-type phosphatase variants are under discordant control of synthesis in human tumor cells. Finally, specific antibodies will be used for tumor localization using I125-labelled specific antibodies and tumor treatment using unlabelled antibodies in the xenograft model. Fluorescein-conjugated and peroxidase-conjugated antibodies will be used in collaborative studies on enzyme localization in tumor cells.